Endogenous DAMPs, Category II: Constitutively Expressed, Injury-Modified Molecules (Cat. II DAMPs)

Abstract

This chapter presents a collection of endogenous DAMPs in terms of constitutively expressed injury-modified molecules. The first class of this category refers to DAMPs released from the extracellular matrix. These molecules are defined to operate as bona fide DAMPs in the form of proteolytically cleaved fragments released as soluble modified proteins into the circulation. They include subclasses such as proteoglycans, glycosaminoglycans, and glycoproteins. The second class of this category refers to molecules, which act as cell-extrinsically expressed modified DAMPs. Subclasses of this class include membrane-bound oxidation-specific epitopes, which act as both antigens to be recognized by host T cells and DAMPs sensed by various pattern recognition molecules to promote innate immune responses, membrane-bound modified structural sugar patterns, and plasma-derived modified soluble molecules such as oxidized low-density lipoprotein. The third class refers to molecules, which operate as cell-intrinsically expressed modified DAMPs. Subclasses include nuclear DNA breaks, cytosolic mislocated/dislocated nuclear and mitochondrial DNA, cytosolic abnormally accumulating RNA, dyshomeostasis-associated perturbed molecular patterns such as reflected by intracellular potassium efflux, and accumulating metabolic molecules such as succinate.

All these DAMPs are of different structure, localization, and function and are sensed by various pattern recognition receptors. It is concluded that evolution, from the very beginning, has apparently taken care to furnish damaged mammalian cells with clear-cut stigmatic markers which enable the sensing molecules to properly recognize them. Such markers act as DAMPs to signal any infectious or sterile intracellular perturbation, cell stress, and tissue injury, wheresoever they are located and whatsoever their distinct nature is.